Medicaments have been packaged in containers such as glass vials with rubber stoppers for many years. As concern for package integrity and other packaging considerations have increased, various improvements have been adopted to provide more satisfactory container assemblies. One such development was the use of aluminum and other metal or metal alloys as a cap seal, where the aluminum seal is crimped or curved around the finish of the vial to hold the rubber stopper firmly in place. While this has been found to be ideal in some circumstances, aluminum seals are not the universal answer to all medical packaging concerns.
One particular packaging endeavor in the medical industry where aluminum seals have provided disadvantages as well as advantages is in lyophilization procedures where the stopper is partially inserted into the vial before a lyophilization procedure, followed by complete insertion of the stopper into the vial. Aluminum seals have prevented efficient lyophilization because it is difficult to apply a suitable crimp to the seal after the lyophilization step. In addition, silicone or some other lubricant is needed to insure adequate sealing. Finally, aluminum and other metals produce small particles when handled which are difficult to keep out of vials being filled, requiring inspection or other expensive product control steps. It would be of great advantage in the medical product packaging industry if an effective seal could be provided which does not employ aluminum or other metals as sealing elements.
The lyophilization process itself is one which requires a great deal of precise control if efficiencies and economies are to be achieved. Particularly important is the rate of lyophilization, which must be controlled at a rate which does not damage or otherwise affect the drugs or other contents and yet which is as rapid as possible for economic reasons. It is always desirable to balance efficiency with effectiveness, so that the best possible product for the best possible price is produced. An improved design will be of great advantage in the packaging of medicament.
One of the difficulties incurred in packaging medicaments generally and in lyophilization processes in particular is the use of excess force to insert the stopper into the vial. One can visualize the effect of excessive stopper insertion force by picturing the shattering of a glass vial into countless particles. This is always to be avoided. The other end of this concern is that not enough force will be used to insert the stopper and thus the stopper will not properly seal the container.
Stoppering machines have been provided which control the amount of force used on the stopper, so that minimum and maximum amounts of force are controlled. The concern always exists, however, that a particular glass and rubber combination will be so far to the outer limits of manufacturing tolerances for each that failure will still occur. It would be of significant advance in the art if a stopper and container combination could be provided which would permit greater control of the force of insertion, particularly in lyophilization processes which employ a first force to seat the stopper in a lyophilization mode and a second force in the sealing mode.
One prior art device has been proposed which does eliminate the use of metallic seals, and this device is described in U.S. Pat. No. 4,516,684, to Walter. Although the design does eliminate aluminum or other metals, it is not particularly effective for medicaments which must be sealed with the effectiveness of a rubber stopper. As is clear from the Walter patent, a re-sealable closure is provided which is applied to the neck finish of a bottle and where there is a positive locking engagement between the closure and the neck. This is not a design for medical products, however, as the primary use suggested is for motor oil. There is no provision for a really effective seal of the type achieved with rubber stoppers, and, of course, there is no suggestion that a design could be provided which would be useful in a lyophilization process.
Another prior art design which purports to eliminate the need of aluminum or other metal seals is shown in Honma U.S. Pat. No. 4,279,353. Honma described a bottle cap which is wholly made of plastic, where an inner stopper member is made of a flexible plastic material and the outer cap is made of a plastic material which is more rigid than the inner member. The primary feature in Honma which is new is the use of a combination which can be shipped and stored in a combined form so as to be readily pressed into sealing engagement with the bottle neck in the stoppering step without being brought into that relationship inadvertently during that shipping or storage. Honma uses uniformly spaced first and second annular recesses, an integrally downwardly extending inner cylinder, and a pull ring. This design defeats the desirability of being able to seat the stopper portion directly by application of direct force on the entire assembly.
Still another prior art design which has been proposed for use as a closure assembly is Gettig et al U.S. Pat. No. 5,085,332. In this patent, a closure is provided which is one piece in design, where two break-away elements are formed with one of the two elements being displaceable to bias inherently resilient skirt segments about a receptacle rim. The device functions by means of an outwardly flared skirt portion which is biased inwardly by an overlying outer sleeve. The one piece design is intended for use with a stopper which includes a plug portion down into the neck of the vial, thereby preventing effective access to the contents before complete closure of the assembly, even before movement of the outer sleeve to the locking position. Gettig et al does not provide for access to the container when the stopper is inserted because of the plug. More importantly, particularly where glass is the only acceptable container and because glass finishes have a notorious degree of variation in tolerances, the Gettig et al device does not provide an effective seal in lyophilization closure assemblies.
It is an important need in the lyophilization process to eliminate a secondary stoppering step, but that has not been possible to date. Ideally, it would be a great advantage in the art if full stoppering could be done in the lyophilization chamber. The benefits of this advantage would be that the process could be practiced without the use of silicone, because the process would eliminate handling of the stopper after the lyophilization chamber.
Accordingly, it is an object of this invention to provide such a process.
It is also an object of the present invention to provide an effective seal for drug packaging which does not employ aluminum or other metals as sealing elements.
Yet another object of the present invention is to balance efficiency with effectiveness by providing an improved seal for lyophilization packaging.
Another object of the present invention is to provide a stopper and container combination which would permit greater control of the force of insertion, particularly in lyophilization processes which employ a first force to seat the liner or stopper in a lyophilization mode and a second force in the sealing mode.
Still another object of the present invention is to provide a design which permits the desirability of being able to seat the liner or stopper portion directly by application of direct force on the entire assembly.
One important object of the present invention is to provide a closure device which permits an effective seal for serum closure assemblies and particularly for lyophilization closure assemblies using standard glass.
Other objects will appear hereinafter.